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Research Article

预测肝癌预后和耐药的CD8_+T细胞相关基因标记物的综合scRNA-seq分析及鉴定

卷 31, 期 17, 2024

发表于: 01 November, 2023

页: [2414 - 2430] 页: 17

弟呕挨: 10.2174/0109298673274578231030065454

价格: $65

摘要

背景:肿瘤免疫浸润细胞的异质性在肝细胞癌(HCC)的治疗反应和预后中起决定性作用。本研究探讨不同亚型CD8+T细胞对HCC肿瘤微环境及预后的影响。 方法:基于GEO、TCGA和HCCD18数据库获取LUAD患者的单细胞RNA测序、转录组和单核苷酸变异数据。通过一致聚类分析鉴定CD8+ T细胞相关亚型，并使用WGCNA鉴定与预后CD8+ T细胞亚型相关性最高的基因。使用ssGSEA和ESTIMATE算法计算不同亚型之间的途径富集评分和免疫细胞浸润水平。最后，利用TIDE算法、CYT评分和肿瘤反应性评分预测患者对免疫治疗的反应。 结果:基于scRNA- seq数据集(GSE149614)，我们定义了3个CD8+T细胞簇(CD8_0, CD8_1, CD8_2)。其中CD8_2是HCC预后相关危险因素。我们从CD8_2中筛选出30个预后基因，鉴定出3个分子亚型(cluster1, cluster2, cluster3)。cluster1有更好的生存结果，更高的基因突变和增强的免疫浸润。此外，我们发现了12个基因特征(包括CYP7A1、SPP1、MSC、CXCL8、CXCL1、GCNT3、TMEM45A、SPP2、ME1、TSPAN13、S100A9和NQO1)对HCC预后具有良好的预测能力。此外，免疫浸润程度较高的高分患者从免疫治疗中获益较少。评分低的患者对Parthenolide、Shikonin等多种药物的敏感性显著高于评分高的患者。此外，得分高的患者氧化应激途径得分较高，且RiskScore与氧化应激途径得分密切相关。该图具有良好的临床应用价值。 结论:为了预测HCC的生存结果和免疫治疗反应，我们基于CD8+ T细胞的异质性建立了12个基因标记。

关键词: CD8+T细胞，肝细胞癌，scRNA-seq，免疫浸润，parthenolide，甲基化。

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